Neuropeptide maturation

Cortistatin is synthesized as a precursor of 116 amino acids that gives rise to a C-terminal mature peptide, cortistatin-14 (CST-14), that shares 11 of its 14 residues with the neuropeptide somatostatin. However, the similarities between cortistatin and somatostatin are restricted to the mature peptides, which are the products of different genes. CST-14 binds to all five somatostatin receptors in vitro, although several authors suggest that CST-14 exerts its actions in vivo by binding to its own specific receptor (Spier de Lecea, 2000). 

As secretory vesicles mature, many secretory polypeptides undergo post-translational modifications. Many hormones and neuropeptides as well as hydrolytic enzymes are synthesized as inactive polypeptide precursors that need to undergo proteolysis to become active. This maturation process usually starts in the TGN and continues in the secretory vesicles, but may be completed in the extracellular space soon after exocytosis takes place in some cases. The maturation process for neuropeptides is described in Chapter 18. 

Further support for the occurrence and activity of neuropeptides in flatworms stems from the presence of enzymes necessary for the production of the mature peptides. For example, the first step in the generation of a mature neuropeptide is often the excision of a propeptide from a longer pre-propeptide. This is achieved by the activity of prohormone convertases, and a number of putative platyhelminth convertase-encoding cDNAs are represented within the EST databases. 

A striking feature of neurotransmitter ch istry is the precise regulation of synthesis, that, for example, results in a few neurons synthesizing a particular neuropeptide while all the rest do not. It appears from the vertebrate literature that mature neurons also precisely regulate the rate of neuropeptide synthesis... 

Figure 1 Peptide neurotransmitters in the brain. Neuropeptides in the brain function as peptide neurotransmitters to mediate chemical communications among neurons. Neuropeptides are synthesized within secretory vesicles that are transported from the neuronal cell body via the axon to nerve terminals. The proneuropeptide (or prohormone) is packaged with the newly formed secretory vesicle in the cell body, and proteolytic processing of the precursor protein occurs during axonal transport and maturation of the secretory vesicle. Mature processed neuropeptides are contained within secretory vesicles at the synapse where activity-dependent, regulated secretion of neuropeptides occurs to mediate neurotransmission via neuropeptide activation of peptidergic receptors.

These are cell surface molecules which are found on all mature a/fi TcR-positive cells, where they are expressed in a mutually exclusive manner, as well as on both a//3 TcR-positive and a//3 TcR-negative immature thymocytes, where they are coexpressed [145,146]. CD4 has also been found to be expressed in the brain in a pattern which is conserved in primates as well as in rodents and which is suggestive of that of a neuropeptide receptor [147]. Since CD4 has been shown to function as a receptor for HIV-1 [148], its pattern of tissue distribution is consistent with the pathological and clinical findings in HIV-1 infections (acquired immune deficiency syndrome). 

Like JH III in insects, MF seems to play a role in enhancing crustacean reproductive maturity, as well as maintaining the juvenile morphology [123]. The synthesis of JH HI in insects is also regulated by neuropeptides, one group of regulators (the allatostatins) is, in fact, similar in structure to neuropeptides that have been isolated from crustaceans (see Section 3.3) but there is no structural resemblance between the allatostatins and the MOIHs and there is no report on the role of allatostatins in regulating the crustacean MOs. 

Azmitia, E.C. and de Kloet, E. (1987) ACTH neuropeptide stimulation of serotonergic neuronal maturation in tissue culture modulation by hippocampal cells. Prog. Brain Res. 72 311-318. 

For a growing number of neurotransmitters, direct neurotrophic actions have been reported (for a review see Schwartz, 1992 Schwartz and Tani-waki, 1994). These transmitters are serotonin, acetylcholine, norepinephrine, glutamate and endogenous opioid peptides. Some of these neurotrophic transmitters may also be produced by astrocytes. The family of neurotransmitters synthesized by astrocytes comprises y-aminobutyric acid, glutamate, proenkephalin, neuropeptide Y, somatostatin and others. Martin (1992) has coined the term gliotransmitter for such substances. The role of gliotransmission in development and function of the mature nervous system has not been firmly established yet. It can be anticipated, however, that neurotrophic activity of astroglia-derived transmit-... 

B. Dozin and Ph. De Nayer. Nuclear receptors and cytosolic binding sites for triiodothyronine in rat brain and liver during maturation. Effects of neonatal hypothyroidism, Neuropeptides and Psychosomatic Processes", Endroczi et al., eds.. The Hungarian Academy of Sciences, Budapest (1982). 

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